Wang Qi, Qiao Xue, Liu Chun-fang, Ji Shuai, Feng Lin-Min, Qian Yi, Guo De-An, Ye Min
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
J Pharm Biomed Anal. 2014 Sep;98:287-95. doi: 10.1016/j.jpba.2014.06.001. Epub 2014 Jun 6.
Glycycoumarin is a major bioactive coumarin of licorice (Glycyrrhiza uralensis), one of the most popular herbal medicines worldwide. In this work, the metabolism of glycycoumarin in rats was investigated. After oral administration of 40mg/kg glycycoumarin, 4 and 10 metabolites were respectively detected in rats plasma and urine samples by liquid chromatography coupled with mass spectrometry (LC/MS). These metabolites were tentatively characterized by analyzing their tandem mass spectra and high-resolution mass spectra, and the structures of glucuronides were confirmed by β-glucuronidase hydrolysis. Glycycoumarin mainly undertakes hydroxylation and glucuronidation metabolism, accompanied by hydrogenation and dehydrogenation as minor reactions. Two hydroxylated metabolites, 4''-hydroxyl glycycoumarin and 5''-hydroxyl glycycoumarin, were obtained by microbial transformation of Syncephalastrum racemosum AS 3.264, and their structures were fully identified by 1D and 2D NMR. Both metabolites are new compounds. Furthermore, they were proved to be catalyzed by P450 enzymes by rat liver microsomes incubation experiments. Finally, a metabolic pathway of glycycoumarin in rats was proposed. This is the first systematic study on metabolites identification of glycycoumarin.
甘草香豆素是甘草（Glycyrrhiza uralensis）中的一种主要生物活性香豆素，甘草是全球最受欢迎的草药之一。在本研究中，对甘草香豆素在大鼠体内的代谢进行了研究。口服给予40mg/kg甘草香豆素后，通过液相色谱-质谱联用（LC/MS）在大鼠血浆和尿液样本中分别检测到4种和10种代谢产物。通过分析它们的串联质谱和高分辨质谱对这些代谢产物进行了初步表征，并通过β-葡萄糖醛酸酶水解确认了葡萄糖醛酸苷的结构。甘草香豆素主要进行羟基化和葡萄糖醛酸化代谢，同时伴有少量的氢化和脱氢反应。通过总状毛霉AS 3.264的微生物转化获得了两种羟基化代谢产物，4''-羟基甘草香豆素和5''-羟基甘草香豆素，并通过一维和二维核磁共振对其结构进行了完全鉴定。这两种代谢产物均为新化合物。此外，通过大鼠肝微粒体孵育实验证明它们是由P450酶催化的。最后，提出了甘草香豆素在大鼠体内的代谢途径。这是首次对甘草香豆素代谢产物鉴定进行的系统研究。
